Sunday, June 10, 2018

JVI: Divergent Human Origin influenza Viruses Detected In Australian Swine Populations


While there is always a concern that a purely zoonotic virus - like SARS, Nipah, or MERS-CoV - could make the leap from an animal host to humans, hybrid flu viruses - reassortants that derive some of their genes from humanized flu - probably have an edge in the pandemic sweepstakes. 
And while we've looked at the potential for dogs and cats - which have frequent contact with human and other flu viruses - serving as a `mixing vessel' for influenza (see mBio: Novel Reassortant Influenza A Viruses in Canines in Southern China), pigs, because of their susceptibility to swine, avian, and human flus, are likely the greatest threat.
Last weekend, in The `Other' Novel Flu Threat We'll Be Watching This Summer, we reviewed the emergence - over the past dozen years - of a number of swine variant viruses, including the highly concerning EAH1N1 virus in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).
But we know little about most of the swine flu viruses that circulate in pigs around the globe. Surveillance is non-existent in much of the world - and as we saw in 2009 - a human adapted swine flu virus can spread quickly, and with little warning.
Over the past decade we've seen plenty of evidence of current (or recent) human flu viruses reassorting with swine flu viruses, but today we've a report from the Journal of Virology with a bit of an unexpected twist.

Researchers have discovered genetic remnants of much older human flu strains still circulating in geographically isolated swine populations in Australia. Lineages going back roughly 50 years (to H3N2 in 1968), which show unexpectedly little antigenic drift over time. 
The authors go on to suggest that `. . . .  isolated swine populations can act as ‘antigenic archives’ of human influenza, raising the risk of re-emergence in humans when sufficient susceptible populations arise.'
The full article is behind a pay wall, but the abstract gives us plenty to chew on.  I'll return with brief postscript.

Divergent human origin influenza viruses detected in Australian swine populations
Frank Y. K. Wong1*, Celeste Donato2, Yi-Mo Deng3, Don Teng2, Naomi Komadina3, Chantal Baas3, Joyanta Modak2, Mark O'Dea4, David W. Smith5,6, Paul V. Effler6,7, Julie Cooke1, Kelly R. Davies1, Aeron Hurt3, Nina Kung8, Avram Levy5,6, Richmond Loh9, Songhua Shan1, Mustaghfira W. Shinwari8, Vittoria Stevens1, Joanne Taylor1, David T. Williams1, James Watson1, Debbie Eagles1, Sam McCullough1, Ian G. Barr3 and Vijaykrishna Dhanasekaran2,3,10*

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment.
Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia during 2012–2016 from two geographically isolated swine populations in the states of Queensland and Western Australia.
Phylogenetic analysis with an expansive human and swine influenza virus dataset comprising >40,000 sequences sampled globally, revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including H1N1/1977, H1N1/1995, H3N2/1968, H3N2/2003, and H1N1pdm09, and a genotype that contained gene segments derived from the past three pandemics (1968, re-emerged 1977 and 2009).
Of the six human-derived gene lineages only one comprising two viruses isolated in Queensland during 2012 was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3–44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine during 2012–2016.
The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as ‘antigenic archives’ of human influenza, raising the risk of re-emergence in humans when sufficient susceptible populations arise.

IMPORTANCE We described the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations during 2012–2016, showing that these viruses were distinct to each other and to those isolated from swine globally. Whole genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons.
We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated at various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza for extensive periods, we showed direct evidence of a sustained transmission for at least 4 years between 2012–2016.

The progression of human influenza pandemics over the past 130 years is believed to have been H2, H3, H1, H2, H3, H1, H1 . . .
  • H2N2 sparked two pandemics (1898 and 1957) roughly 69 years apart.   
  • H3 viruses unleashed two pandemics (1900 and 1968) roughly 68 years apart
  • And H1N1 caused the great 1918 pandemic only to return in the pseudo-pandemic of 1977, 59 years later (and then reinvented itself in the 2009 Pandemic).
There are some researchers who propose that H2N2 - last seen in 1968, and supplanted by H3N2 after a brief 11 year run - is the logical `next pandemic' strain.

In 2011, after the furor over the 2009 H1N1 pandemic had finally died down, some researchers suggested it might make sense to add an H2N2 component to the seasonal vaccine to head off the `next' pandemic (see Nature: A Preemptive H2N2 Vaccine Strike?).
While it sparked some academic discussions, this controversial proposal never went anywhere, the consensus being it was impossible to pick the `next' pandemic subtype with any confidence. 
In 2012, in H2N2: What Went Around, Could Come Around Again, we looked at a study conducted by researchers at St. Jude Children's Research Hospital - published in the Journal of Virology - that concluded that H2N2 - which persists in wild birds - could pose a threat to humanity once again.

And just last year, in H2N2: Everything Old Is Flu Again, we saw a study published in The Journal Of Veterinary Medical Science, which detailed the finding of H2N2 in Siberian Muskrats. (see Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia).
While geographically isolated swine populations are less common today than they were 50 or 100 years ago, they do still exist; particularly in parts of Asia, South America, and Africa. Added to these are huge numbers of feral swine around the world.
It now appears possible that they could serve as repositories of old flu strains, which are quietly biding their time until levels of community immunity drop to the point where they could once again pose a pandemic threat. 
And if so, this might go a long way in explaining the repeating pattern of H1, H2, and H3 pandemics over the past 130 years.
But of course, patterns - once you think you've identified them - have an annoying habit of changing without warning. Which means I wouldn't discount any of the dozens of other pandemic flu contenders in the wild just yet.